ArticleAmerican journal of cancer research2015
Phospho-4e-BP1 and eIF4E overexpression synergistically drives disease progression in clinically confined clear cell renal cell carcinoma.
Article in American journal of cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Quantitative Proteomics Unveils the Synergistic Effects of Combination Drugs on Cytoskeleton Composition and Autophagy-Mediated Cell Death in Neuroblastoma.Journal of proteome research · 2025Article
- Unraveling the role of PBK in glioblastoma: from molecular mechanisms to therapeutic targets.Annals of medicine and surgery (2012) · 2024Article
- Tumor Necrosis Factor Receptor-2 Signals Clear-Cell Renal Carcinoma Proliferation via Phosphorylated 4E Binding Protein-1 and Mitochondrial Gene Translation.The American journal of pathology · 2024Article
- Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity.Exploration of targeted anti-tumor therapy · 2023Article
- Discovery of pathway-independent protein signatures associated with clinical outcome in human cancer cohorts.Scientific reports · 2022Article
- The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review.Cancers · 2021Review
- Permutation-based identification of important biomarkers for complex diseases via machine learning models.Nature communications · 2021Article
- RUNX1/miR-582-5p Pathway Regulates the Tumor Progression in Clear Cell Renal Cell Carcinoma by Targeting COL5A1.Frontiers in oncology · 2021Article
- Clinical implications of intratumor heterogeneity: challenges and opportunities.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Impact of eIF4E phosphorylation at Ser209 via MNK2a on tumour recurrence after curative surgery in localized clear cell renal cell carcinoma.Oncotarget · 2019Article
- Expression of total and phospho 4EBP1 in metastatic and non-metastatic renal cell carcinoma.Oncology letters · 2019Article
- Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies.Molecular cancer therapeutics · 2018Review
- Inhibition of eIF4E cooperates with chemotherapy and immunotherapy in renal cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Article
- Review
- Article
- Expression of 4E-BP1 and phospho-4E-BP1 correlates with the prognosis of patients with clear cell renal carcinoma.Cancer management and research · 2018Article
- Downregulation of microRNA-15a suppresses the proliferation and invasion of renal cell carcinoma via direct targeting of eIF4E.Oncology reports · 2017Article
- Prognostic significance of eukaryotic initiation factor 4E in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2016Article
- Phosphorylated 4EBP1 is associated with tumor progression and poor prognosis in Xp11.2 translocation renal cell carcinoma.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clear cell renal cell carcinoma (ccRCC), the most aggressive and lethal form of renal cell carcinoma accounts for over 90% of metastasis that occur following curative surgery for clinically confined disease. High relapse rates have prompted the evaluation of targeted therapies for the prevention or delay of metastatic disease in high-risk patients, with biomarkers offering significant potential to guide and improve patient management in this setting. In this current study we examined the value of the 4E-BP1/eIF4E axis for prognostic significance and risk stratification in patients with clinically confined ccRCC. This axis is a critical convergence point for many signalling pathways that are targeted by current therapies for the treatment of advanced RCC. Immunohistochemistry for phosphorylated 4E-BP1 (p4E-BP1) and total eIF4E was performed on tissue microarrays containing tumour cores from 135 patients with localised ccRCC. For both biomarkers 39% of all evaluable cores stained positive, with a strong correlation observed between the presence of p4E-BP1 and the overexpression of eIF4E within the same tumour (P = 0.005). Further, the combined expression of p4E-BP1 and eIF4E was associated with significantly worse disease-free survival of 2.9 vs 5.7 yrs compared to patients whose tumours expressed only one, or neither, of the biomarkers (P < 0.001). Cox-regression analysis confirmed the ability of the p4EBP1/eIF4E signature to independently identify high-risk patients with a Hazard Ratio of 4.2 (CI = 2.1-8.6; P < 0.001), compared to 3.3 for tumour grade 3 and 4, and 2.3 for tumour stage 3 and 4. These data show the powerful prognostic value of the p4E-BP1/eIF4E signature for potential management of patients with clinically confined ccRCC, and in addition provides insights into the possible key synergistic determinants of disease progression and treatment response.
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Identifiers
26609489PMC4633910W2207627189What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.